We sequenced exomes from more than 2,500 simplex families each having a child with an autistic spectrum disorder (ASD). By comparing affected to unaffected siblings, we estimate that 13% of de novo (DN) missense mutations and 42% of DN likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding DN mutations contribute to about 30% of all simplex and 45% of female diagnoses. Virtually all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower IQ, but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to causative missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Virtually all significance for the latter comes from affected females.

SUMMARY Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.

Chronux is an open-source software package developed for the analysis of neural data. The current version of Chronux includes software for signal processing of neural time-series data including several specialized mini-packages for spike sorting, local regression, audio segmentation, and other data-analysis tasks typically encountered by a neuroscientist. Chronux is freely available along with user tutorials, sample data, and extensive documentation from http://chronux.org/.

The third edition of the joint British Transplantation Society/Renal Association guidelines for living donor kidney transplantation was published in May 2011. The guideline has been extensively revised since the previous edition in 2005 and has used the GRADE system to rate the strength of evidence and recommendations. This article summarizes the statements of recommendation contained in the guideline, which provide a framework for the delivery of living kidney donation in the United Kingdom and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at http://www.bts.org.uk/transplantation/standards-and-guidelines/ and http://www.renal.org/clinical/OtherGuidelines.aspx (transplantation is welcome to add a web link in this article to/through its own Web site to increase traffic).

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